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Block Effect of Capsaicin on the Human HERG Potassium Currents Was Enhanced by S6 Mutation at Y652
Author: XingJunLian
Tutor: MaJiZuo
School: Wuhan University of Science and Technology
Course: Physiology
Keywords: Capsaicin HERG Potassium channel Voltage clamp
CLC: R33
Type: Master's thesis
Year: 2009
Downloads: 43
Quote: 0
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Abstract
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Objective: To study of capsaicin on the wild-type and mutant HERG ion channel blocking effect, an attempt to explore in S6 domain mutation point is the important role of capsaicin combined with HERG loci . Methods: A two-electrode voltage clamp technique was HERG ion channel currents expressed in Xenopus laevis oocytes ( wild-type , Y652A , F656A type) . Results: Capsaicin blocks wild-type HERG potassium channel current in a concentration-dependent manner , and its half maximal effect concentration (IC50) 17.45μM . Capsaicin blocking 50% of the maximal activation of wild -type HERG channel potential does not change , but the steady-state inactivation curves to a negative drift . Capsaicin HERG channel can be blocked off and open the two states . However , compared with wild-type HERG channel blocking Y652 amino acid residue mutations significantly enhanced its blocking action is alanine , an IC50 of 5.68μM F656A mutation and wild-type blocking effect was not significantly difference. Meanwhile, we have also found that the use of 25μM capsaicin , Y652A type channel steady-state activation to the positive drift 5mV, and deactivation parameters to drift to the negative direction of increasing the - 29mV . Conclusion: capsaicin binding and blocking of the closed and open state of the HERG channel , S6 domain Y652 is located in the point of the most significant bits of the channel with capsaicin . Capsaicin Y652A mutant HERG channel blocking effects significantly stronger than the wild type , suggesting that channel mutation may cause some patients in the clinical particularly sensitive to capsaicin .
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